Project Summary Adolescent substance use is a prevalent and significant public health concern. Although gains have been made in the development of effective substance use preventive interventions, there is room for improvement. Intervention refinements must be based on additional longitudinal research of developmental precursors that emerge well before substance use onset. Deficits in executive control (EC), a set of cognitive abilities for directing attention and behavior, have been proposed as important and modifiable contributors to adolescent problem behaviors, including substance use as well as co-occurring externalizing and internalizing problems. However, the early-emerging and dynamically-unfolding role of EC in the development of substance use and related problems is not well understood. Existing research lacks a long-term, developmentally-nuanced perspective, precluding an understanding of when and how poor EC impacts substance use risk. Preschool is a time of significant EC organization. Adolescence is a time of further EC development and differentiation, and the emergence of substance use. Yet, relevant studies spanning these critical developmental periods are lacking. This application proposes to extend an ongoing study of young children and their parents followed during preschool and the elementary school years with intensive, repeated, performance-based measures of EC (along with multi-rater, multi-method assessments of a broad array of additional factors) by collecting new data at ages 14, 15, 16, and 17. The long-term goal is to guide the development and refinement of substance use preventive interventions targeting EC as a modifiable risk factor at critical points in development. The objective of the proposed research is to explicate the long-term, dynamic impact of EC on the development of substance use and co-occurring problems. The central hypotheses are that poor EC in preschool, throughout childhood, and into adolescence will be related to the onset and growth of substance use and problem co- occurrence, and that these associations will be at least partially mediated by social developmental processes. The rationale is that a nuanced, longitudinal study of EC and substance use will richly inform the timing and targets of interventions focusing on EC to prevent adolescent substance use and related problems. The specific aims are to examine the long-term impact of EC in preschool (Aim 1) as well as the development of EC throughout childhood and adolescence (Aim 2) on adolescent substance use and co-occurring internalizing and externalizing problems, testing family, school, and peer mediating mechanisms (Aim 3) and exploring gender moderation (Exploratory Aim). The proposed project is innovative in its unique leveraging of early EC data from the sample and its rigorous and multifaceted measurement of EC over critical developmental periods. The significance of this research is that it will yield an unprecedented understanding of the impact of EC on substance use, affording new insights into when and how EC has its effects and providing information for designing optimally-timed, targeted interventions to bolster EC and prevent adolescent substance use.